The longterm objective of this research has been the development of a system for classifying the depressive disorders, based on a knowledge of the biochemical and pathophysiological processes underlying different types of depressions, in order to provide criteria for more specific and effective treatment. The proposed research on the depressive disorders aims: a) to extend our findings that pretreatment baseline levels of urinary MHPG can predict response to tricyclic and tetracyclic antidepressants (including maprotiline, C-49802B-Ba, amitriptyline and imipramine); b) to explore the possibility that for any given antidepressant drug, patients with different biochemical subtypes of depressions may differ with respect to the duration of drug administration, as well as the minimum dosage and blood levels required for a favorable antidepressant response; c) to continue longitudinal studies of the biochemical changes that occur during tricyclic and tetracyclic antidepressant drug treatment, and in particular to extend our findings of differences in patterns of change in urinary MHPG levels observed in responders versus nonresponders; d) to explore further aspects of the findings that platelet MAO activity shows significant MAO inhibitors, and to test the hypothesis that high pretreatment platelet MAO activity predicts favorable response to MAO inhibitors; e) to extend our findings that subgroups of depressive disorders are meaningfully differentiated on the basis of biochemical criteria, and in particular to examine the clinical, physiological and biochemical features of the subgroup of unipolar depressions characterized by elevated urinary MHPG levels. In addition to studies of urinary catecholamines and metabolites in depressive disorders, this research will include studies of: alpha-adrenergic receptor function in platelets; beta-adrenergic receptor function in leukocytes; platelet MAO; platelet serotonin uptake; plasma and urinary cortisol levels; dexamethasone suppression test responses; and plasma levels of the tricyclic and tetracyclic antidepressant drugs used in this research.